It is proposed to conduct clinical testing of the efficacy of a red blood cell ghost (RBCG) "Trojan Horse" drug delivery system for the iron chelator desferrioxamine (DF) in patients with iron overload. RBCGs are taken up by reticuloendothelial cells of the spleen and liver, the major sites of iron deposition in thalassemia and other iron loading anemias. We have demonstrated marked enhancement of DF-induced iron excretion in hypertransfused rats when DF is entrapped in RBCGs compared to intravenous or slow subcutaneous injection of free DF. We have also demonstrated the feasibility of loading sufficient DF into human RBCGs to administer doses of the drug. We shall compare urinary iron excretion following a dose of DF entrapped in RBCGs to the same dose of free DF administered by intramuscular, intravenous or slow subcutaneous injection. Other aspects of this targeted delivery of DF will be studied. Dose effectiveness of DF given in RBCGs will be assessed by measuring urinary iron output in response to graded doses of the chelator. The potentially enhancing effects of ascorbic acid on release of iron for chelation will be investigated by comparison of DF entrapped in RBCG and without ascorbate. Possible tachyphylaxis will be investigated by determining if there is any progressive diminution in the amount of iron chelated by a standard dose of DF in RBCG when it is repeatedly exhibited to a patient. Patients will include those with thalassemia major, other iron loading anemias caused by periodic blood transfusion and idiopathic hemochromatosis. Patients will serve as their own controls and their own red cells will be used for making RBCGs. An adjunct to this work will include laboratory experiments to improve and optimize conditions for getting high concentrations of DF into RBCGs. We are seeking to develop this technique as a potential improvement of existing methods to treat the iron overload of thalassemia and related conditions. We also anticipate that these studies will provide useful information concerning the source and availability for chelation of iron in different storage sites.